Tumor Suppressor Function of CYLD in Nonmelanoma Skin Cancer
Downregulation of CYLD in BCC mediated by hedgehog signaling pathway. In the absence of ligand, the hedgehog (Hh) signaling pathway is inactive (left). Patched (PTCH) inhibits the activity of Smoothened (SMO), which in turn is unable to activate GLI transcription factors through interactions with FUSED and Suppressor of FUSED (SUFU). The binding of SUFU also prevents the transcription of Hh target genes. Binding of the Hh ligand inhibits PTCH and activates hedgehog pathway (right) through derepression of SMO and translocation of GlLI to the nucleus. Nuclear GLI activates target gene expression, including PTCH, GLI, and Snail. Expression of Snail leads to transcriptional inactivation of CYLD by recruitment of Snail to the CYLD promoter.